It is our aim to eluciated mechanisms of amino acid metabolism in normal man and in experimental animals as well as in patients with metabolic disorders. We will carry out these experiments using stable isotopes, gas chromatography, mass spectrometry (GC/MS), and other analytical methods. two major directions, each consisting of several projects, will be pursued toward this goal. the first is to study the mechanisms of some unknown steps in the metabolism of lysine, isoleucine, and valine. This will be done in patients with inborn metabolic disorders, as well as in experimental animals, by using compounds labeled with stable isotopes. The second is to develop new sensitive analytical methods, using the stable isotope dilution and GC/MS, to be utilized for prenatal diagnosis and heterozygote identification of inborn disorders of amino acid metabolism. With these two types of approaches, we hope to obtain new information directly concerning the betterment of patients with disorders of amino acid metabolism, and to contribute new knowledge for a clearer understanding of normal human physiology.